Polyvinylpyrrolidone for the stabilization of a solid dispersion of the non-crystalline form of rotigotine

Abstract

The present invention relates to a method for stabilizing rotigotine, the method comprising providing a solid dispersion comprising polyvinylpyrrolidone and a non-crystalline form of rotigotine, wherein the weight ratio of rotigotine to polyvinylpyrrolidone is in a range from about 9:3.5 to about 9:6. The present invention also relates to a solid dispersion comprising a dispersing agent and a dispersed phase, said dispersed phase comprising rotigotine and polyvinylpyrrolidone, wherein the weight ratio of rotigotine to polyvinylpyrrolidone is in a range from about 9:3.5 to about 9:6, a pharmaceutical composition comprising such a solid dispersion, in particular a transdermal therapeutic system, as well as a method for the preparation thereof.

The invention claimed is: 
     
       1. A method for stabilizing rotigotine, the method comprising providing a solid dispersion comprising polyvinylpyrrolidone and a non-crystalline form of rotigotine free base, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is about 9:4. 
     
     
       2. A solid dispersion comprising a dispersing agent and a dispersed phase, said dispersed phase comprising rotigotine free base and polyvinylpyrrolidone, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is about 9:4. 
     
     
       3. The solid dispersion of  claim 2 , wherein the solubility of rotigotine free base in the dispersing agent is below 1 wt-%. 
     
     
       4. The solid dispersion of  claim 2 , wherein the dispersing agent comprises at least one silicone pressure sensitive adhesive. 
     
     
       5. The solid dispersion of  claim 2 , wherein the dispersing agent comprises a mixture of a first silicone pressure sensitive adhesive and a second silicone pressure sensitive adhesive and wherein the solid dispersion has a complex viscosity between 5 and 15 MP. 
     
     
       6. The solid dispersion of  claim 2 , wherein rotigotine free base and polyvinylpyrrolidone are in a multitude of microreservoirs. 
     
     
       7. A pharmaceutical composition comprising a solid dispersion according to  claim 2 . 
     
     
       8. A transdermal therapeutic system comprising at least one amine-compatible silicone pressure sensitive adhesive, about 0.1 to about 3.15 mg/cm 2  of rotigotine in the free base form, and polyvinylpyrrolidone, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is about 9:4. 
     
     
       9. The transdermal therapeutic system of  claim 8 , wherein rotigotine free base and polyvinylpyrrolidone are contained in a multitude of microreservoirs. 
     
     
       10. A transdermal therapeutic system comprising a solid dispersion of  claim 2 . 
     
     
       11. The transdermal therapeutic system of  claim 10 , comprising 0.1 to about 3.15 mg/cm 2  of rotigotine free base. 
     
     
       12. A method for preparing a transdermal therapeutic system, the method comprising preparing a solid dispersion comprising a dispersing agent and a dispersed phase, said dispersed phase comprising rotigotine free base and polyvinylpyrrolidone, wherein the weight ratio of rotigotine free base to polyvinylpyrrolidone is about 9:4. 
     
     
       13. The method of  claim 1 , wherein the solid dispersion further comprises a dispersing agent. 
     
     
       14. The method of  claim 13 , wherein the dispersing agent comprises at least a first adhesive having a complex viscosity between 40 and 250 MP. 
     
     
       15. The method of  claim 14 , wherein the dispersing agent comprises at least a second adhesive having a complex viscosity between 1 and 10 MP. 
     
     
       16. The method of  claim 15 , wherein the dispersing agent has a complex viscosity between 5 and 25 MP. 
     
     
       17. The method of  claim 13 , wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a complex viscosity between 5 and 15 MP. 
     
     
       18. The method of  claim 13 , wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a peel adhesion between 3 and 16N/50 mm at a thickness of 50 g/m 2  and/or a peel adhesion between 14 and 26 N/50 mm at a thickness of 150 g/m 2 . 
     
     
       19. The method of  claim 13 , wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a static shear adhesion between 20 and 150 min. 
     
     
       20. The solid dispersion of  claim 2 , wherein the dispersing agent comprises at least a first adhesive having a complex viscosity between 40 and 250 MP. 
     
     
       21. The solid dispersion of  claim 2 , wherein the dispersing agent comprises at least a second adhesive having a complex viscosity between 1 and 10 MP. 
     
     
       22. The solid dispersion of  claim 21 , wherein the dispersing agent has a complex viscosity between 5 and 25 MP. 
     
     
       23. The solid dispersion of  claim 2 , wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a complex viscosity between 5 and 15 MP. 
     
     
       24. The solid dispersion of  claim 2 , wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a peel adhesion between 3and 16 N/50 mm at a thickness of 50 g/m 2  and/or a peel adhesion between 14 and 26 N/50 mm at a thickness of 150 g/m 2 . 
     
     
       25. The solid dispersion of  claim 2 , wherein the dispersing agent comprises at least a first adhesive and a second adhesive and the solid dispersion has a static shear adhesion between 20 and 150 min.